Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined metalloproteinase (MMP)-1, -2, -3, and -9 mRNA expression by peripheral blood monocytes from 50 patients with immunoglobulin A (IgA) nephropathy, 20 with membranous nephropathy, 10 with minimal-change nephrotic syndrome, five with focal glomerulosclerosis, 30 with non-IgA proliferative glomerulonephritis, and 40 healthy normal controls who were comparable with regard to age and sex. Monocytes from patients with IgA nephropathy expressed a higher level of MMP-9 mRNA than those from patients with other forms of glomerulonephritis or from healthy controls (MMP-9 to glyceraldehyde-3-phosphate dehydrogenase ratio: IgA nephropathy, 1.68 +/- 0.24; membranous nephropathy, 0.22 +/- 0.08; minimal-change nephrotic syndrome, 0.24 +/- 0.06; focal glomerulosclerosis, 0.32 +/- 0.08; non-IgA proliferative glomerulonephritis, 0.30 +/- 0.12; and healthy controls, 0.16 +/- 0.04). When the biopsy specimens were classified into four grades according to the severity of glomerular and interstitial pathology, highly significant differences were observed among MMP-9 mRNA levels in monocytes from all four groups of patients with IgA nephropathy (grade I, 0.44 +/- 0.09; grade II, 1.06 +/- 0.26; grade III, 2.22 +/- 0.68; grade IV, 2.86 +/- 0.88). In addition, MMP-9 mRNA levels from patients with IgA nephropathy correlated with urinary protein excretion (P < 0.001). However, we detected minimal mRNA expression of MMP-1, -2, and -3 by peripheral blood monocytes from patients with IgA nephropathy or other forms of glomerulonephritis and from normal healthy controls. Our results suggest that increased MMP-9 mRNA expression in circulating monocytes may contribute to the progression of IgA nephropathy.
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PMID:Increased mRNA expression of metalloproteinase-9 in peripheral blood monocytes from patients with immunoglobulin A nephropathy. 871 19

Matrilysin, a member of matrix metalloproteinase family, is believed to play a significant role in the growth and proliferation of colon cancer cells. Overexpression of the matrilysin gene has been shown to correlate with Dukes' stage and increased metastatic potential in colorectal cancer. The aim of this study was to evaluate the effect of preoperative high-dose radiotherapy (25 Gy in five fractions over 5 days) on matrilysin (MMP-7) gene expression, in patients with resectable rectal cancer, by a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Biopsy samples of tumour (n=30) and distant normal mucosa (n=12) from 15 patients were obtained pre- and post-radiotherapy. Messenger (m)RNA was extracted from all of the tissue samples and reverse transcribed to double-stranded cDNA. Quantitative RT-PCR was performed to study the effect of preoperative radiotherapy on matrilysin gene expression in both the tumour and normal mucosal specimens. Matrilysin mRNA values were expressed relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for each sample. In 14 out of 15 cases, matrilysin mRNA was detected in the cancerous tissue. Although all six normal mucosal specimens expressed matrilysin mRNA, the levels were approximately 10-fold lower compared with those seen in the paired tumour samples. Preoperative radiotherapy led to a significant 6- to 7-fold increase (P=0.001) in the expression of matrilysin mRNA in rectal cancer tissue. In contrast, there was no significant change in the matrilysin mRNA expression of normal mucosal specimens post-radiotherapy. Preoperative high-dose radiotherapy upregulates matrilysin gene expression in rectal cancer. Matrilysin inhibition may be a useful preventive or therapeutic adjunct to radiotherapy in rectal cancer.
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PMID:Effect of preoperative radiotherapy on matrilysin gene expression in rectal cancer. 1187 42

The purpose of this study was to monitor the expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) produced by an osteoblastic cell line MG63 stimulated with Prevotella nigrescens lipopolysaccharides (LPS), and to compare the level of secretion before and after the P. nigrescens LPS was treated with calcium hydroxide [Ca(OH)2]. The underlying hypothesis is that the balance between MMP and TIMP secretion is the key to an understanding of the host degradative pathways involved in the pathogenesis of bacterial derived pulpal and periapical diseases. Confluent monolayers of MG63 human osteosarcoma cells were exposed to varying concentrations of P. nigrescens or Escherichia coli LPS. Alternately, confluent cultures were exposed to 10 microg/ml of bacterial LPS pretreated with Ca(OH)2 (12.5 mg/ml) for 72 hours. At the end of the experimental period, total RNA was extracted and real-time quantitative polymerase chain reaction (PCR) was performed for MMP-1, TIMP-1, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The results showed that the expression of MMP-1 mRNA was low and invariant for the experimental period in the negative controls. However, exposure to P. nigrescens LPS increased expression after 48 hours. Expression of TIMP-1 mRNA was highly increased at 24 and 48 hours with lower concentrations of LPS in contrast to a suppression with a concentration of 10 microg/ml. Treatment of P. nigrescens LPS with Ca(OH)2 resulted in a down-regulation of MMP-1, whereas pretreated E. coli LPS demonstrated no stimulatory activity for MMP-1 gene expression. Both types of LPS when pretreated with Ca(OH)2 induced slightly up-regulated expression of TIMP-1.
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PMID:Effect of calcium hydroxide-treated Prevotella nigrescens on the gene expression of matrix metalloproteinase and its inhibitor in MG63 cells. 1717 69

Mitochondrial dysfunction causes energy deficiency and nigrostriatal neurodegeneration which is integral to the pathogenesis of Parkinson disease (PD). Clearance of defective mitochondria involves fission and ubiquitin-dependent degradation via mitophagy to maintain energy homeostasis. We hypothesize that LRRK2 (leucine-rich repeat kinase 2) mutation disrupts mitochondrial turnover causing accumulation of defective mitochondria in aging brain. We found more ubiquitinated mitochondria with aberrant morphology associated with impaired function in aged (but not young) LRRK2R1441G knockin mutant mouse striatum compared to wild-type (WT) controls. LRRK2R1441G mutant mouse embryonic fibroblasts (MEFs) exhibited reduced MAP1LC3/LC3 activation indicating impaired macroautophagy/autophagy. Mutant MEFs under FCCP-induced (mitochondrial uncoupler) stress showed increased LC3-aggregates demonstrating impaired mitophagy. Using a novel flow cytometry assay to quantify mitophagic rates in MEFs expressing photoactivatable mito-PAmCherry, we found significantly slower mitochondria clearance in mutant cells. Specific LRRK2 kinase inhibition using GNE-7915 did not alleviate impaired mitochondrial clearance suggesting a lack of direct relationship to increased kinase activity alone. DNM1L/Drp1 knockdown in MEFs slowed mitochondrial clearance indicating that DNM1L is a prerequisite for mitophagy. DNM1L knockdown in slowing mitochondrial clearance was less pronounced in mutant MEFs, indicating preexisting impaired DNM1L activation. DNM1L knockdown disrupted mitochondrial network which was more evident in mutant MEFs. DNM1L-Ser616 and MAPK/ERK phosphorylation which mediate mitochondrial fission and downstream mitophagic processes was apparent in WT using FCCP-induced stress but not mutant MEFs, despite similar total MAPK/ERK and DNM1L levels. In conclusion, aberrant mitochondria morphology and dysfunction associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in mutant LRRK2 MEFs and mouse brain. Abbreviations: ATP: adenosine triphosphate; BAX: BCL2-associated X protein; CDK1: cyclin-dependent kinase 1; CDK5: cyclin-dependent kinase 5; CQ: chloroquine; CSF: cerebrospinal fluid; DNM1L/DRP1: dynamin 1-like; ELISA: enzyme-linked immunosorbent assay; FACS: fluorescence-activated cell sorting; FCCP: carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; LAMP2A: lysosomal-associated membrane protein 2A; LRRK2: leucine-rich repeat kinase 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK1/ERK2: mitogen-activated protein kinase 1; MEF: mouse embryonic fibroblast; MFN1: mitofusin 1; MMP: mitochondrial membrane potential; PAmCherry: photoactivatable-mCherry; PD: Parkinson disease; PINK1: PTEN induced putative kinase 1; PRKN/PARKIN: parkin RBR E3 ubiquitin protein ligase; RAB10: RAB10, member RAS oncogene family; RAF: v-raf-leukemia oncogene; SNCA: synuclein, alpha; TEM: transmission electron microscopy; VDAC: voltage-dependent anion channel; WT: wild type; SQSTM1/p62: sequestosome 1.
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PMID:Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2R1441G mice. 3330 Apr 46